EFNB3

Summary

EFNB3 (ephrin B3, HGNC:3228) is a protein-coding gene on chromosome 17p13.1, encoding Ephrin-B3 (Q15768). Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.

EFNB3, a member of the ephrin gene family, is important in brain development as well as in its maintenance. Moreover, since levels of EFNB3 expression were particularly high in several forebrain subregions compared to other brain subregions, it may play a pivotal role in forebrain function. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH Receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997). Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands.

Source: NCBI Gene 1949 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3228
Approved symbol	EFNB3
Name	ephrin B3
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	LERK-8
Ensembl gene	ENSG00000108947
Ensembl biotype	protein_coding
OMIM	602297
Entrez	1949

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000226091

RefSeq mRNA: 1 — MANE Select: NM_001406 NM_001406

CCDS: CCDS11120

Canonical transcript exons

ENST00000226091 — 5 exons

Exon	Start	End
ENSE00000949192	7707958	7708250
ENSE00000949193	7708435	7708527
ENSE00001061706	7708635	7708739
ENSE00001147200	7705202	7705720
ENSE00001254345	7709167	7711372

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 92.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8659 / max 93.4990, expressed in 1011 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159330	3.5692	920
159331	1.8347	534
159329	0.4620	274

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	92.45	gold quality
cortical plate	UBERON:0005343	92.44	gold quality
nucleus accumbens	UBERON:0001882	90.66	gold quality
endothelial cell	CL:0000115	89.65	gold quality
prefrontal cortex	UBERON:0000451	89.16	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.51	gold quality
ganglionic eminence	UBERON:0004023	88.50	gold quality
frontal cortex	UBERON:0001870	87.64	gold quality
embryo	UBERON:0000922	87.18	gold quality
neocortex	UBERON:0001950	87.18	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.99	gold quality
caudate nucleus	UBERON:0001873	86.85	gold quality
entorhinal cortex	UBERON:0002728	86.84	gold quality
ventricular zone	UBERON:0003053	86.74	gold quality
right frontal lobe	UBERON:0002810	86.73	gold quality
cerebral cortex	UBERON:0000956	86.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.51	gold quality
hypothalamus	UBERON:0001898	86.15	gold quality
cingulate cortex	UBERON:0003027	86.12	gold quality
anterior cingulate cortex	UBERON:0009835	85.88	gold quality
telencephalon	UBERON:0001893	85.78	gold quality
superior frontal gyrus	UBERON:0002661	85.54	gold quality
temporal lobe	UBERON:0001871	84.94	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.64	gold quality
forebrain	UBERON:0001890	84.40	gold quality
parietal pleura	UBERON:0002400	84.05	gold quality
Ammon’s horn	UBERON:0001954	84.02	gold quality
orbitofrontal cortex	UBERON:0004167	83.99	gold quality
hair follicle	UBERON:0002073	83.96	silver quality
putamen	UBERON:0001874	83.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	763.34
E-ANND-3	no	2.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN, RBPJ, TP53

miRNA regulators (miRDB)

114 targeting EFNB3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-548A-3P	99.76	70.58	3524

Literature-anchored findings (GeneRIF, showing 18)

• expressed differentially in colon carcinoma and normal mucosa specimens and may play a role in progression of colon carcinoma (PMID:11920461)
• EphrinB3 is a bona fide alternate receptor for NiV entry, and two residues in the G-H loop of the ephrin B-class ligands are critical determinants of NiV receptor activity. (PMID:16477309)
• Immunohistochemistry shows robust staining for phosphorylated ephrin-B and ephrin-B3 in invading glioblastoma cells. (PMID:16951161)
• Transgenic EphB1 and ephrin-B3 cooperatively regulate the proliferation and migration of neural progenitors in the hippocampus (PMID:18057206)
• report the crystal structures of the NiV-G both in its receptor-unbound state and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor (PMID:18632560)
• evidence for an unknown ephrin-B3-binding cell-surface proteoglycan involved in cellular signalling (PMID:20925654)
• Phosphoproteomic profiling of nonsmall cell lung cancer cells reveals that ephrin B3 regulates pro-survival signaling through Akt1-mediated phosphorylation of the EphA2 receptor. (PMID:21413766)
• Ephrin-B3 binds to B lymphocytes, most likely via a non-classical receptor, and induces migration of the memory B cell subpopulation. (PMID:21447033)
• Data suggest that fusion of Nipah viruses with host cells is facilitated by two of viral membrane proteins, the G protein and the F protein; G head domain binds to human ephrins B2 and B3 altering conformational density of entire G head domain. (PMID:24615845)
• Findings suggest that EphrinB3 may be a relevant target for promoting remyelination in demyelinating disease (PMID:26687980)
• Study found up-regulated expression of ephrinB3/EphB3 in intractable temporal lobe epilepsy patients and experimental temporal lobe epilepsy rats, which suggested that ephrinB3/EphB3 might be involved in the pathogenesis of temporal lobe epilepsy (PMID:26930615)
• Data show that Ephrin B3 was concomitantly expressed with EphA2 and Ephrin A1 with higher Ephrin B3 levels found in non-squamous than in squamous tumors. (PMID:27533087)
• Data suggest that molecules in the erythropoietin-producing hepatocellular receptor B family (EPHB) / ephrinB (EFNB) signalling pathways, specifically ephrin B3 and GRIP1, are involved blood pressure regulation. (PMID:27941904)
• The study provides evidence from single nucleotide polymorphism analyses of ADVANCE study demonstrating that EFNB3 is a hypertension risk gene. (PMID:28272517)
• identified secretory and cell associated proteoglycans with high ability to bind ephrin-B3 and suggest that ephrin-B3 can bind to a protein complex organized by a membrane associated PG. (PMID:29953858)
• Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism. (PMID:30262919)
• Blood vessels guide Schwann cell migration in the adult demyelinated CNS through Eph/ephrin signaling. (PMID:31011859)
• Ephrin B3 exacerbates colitis and colitis-associated colorectal cancer. (PMID:38142837)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	efnb3b	ENSDARG00000042277
danio_rerio	efnb3a	ENSDARG00000112993
mus_musculus	Efnb3	ENSMUSG00000003934
drosophila_melanogaster	Ephrin	FBGN0040324
caenorhabditis_elegans		WBGENE00001163
caenorhabditis_elegans		WBGENE00001164
caenorhabditis_elegans		WBGENE00001165
caenorhabditis_elegans		WBGENE00006869

Paralogs (7): EFNB1 (ENSG00000090776), EFNA2 (ENSG00000099617), EFNB2 (ENSG00000125266), EFNA3 (ENSG00000143590), EFNA1 (ENSG00000169242), EFNA5 (ENSG00000184349), EFNA4 (ENSG00000243364)

Protein

Protein identifiers

Ephrin-B3 — Q15768 (reviewed: Q15768)

Alternative names: EPH-related receptor transmembrane ligand ELK-L3, EPH-related receptor tyrosine kinase ligand 8

All UniProt accessions (1): Q15768

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. May play a pivotal role in forebrain function. Binds to, and induce the collapse of, commissural axons/growth cones in vitro. May play a role in constraining the orientation of longitudinally projecting axons. (Microbial infection) Acts as a receptor for nipah virus and hendra virus.

Subunit / interactions. Interacts with GRIP1 and GRIP2. (Microbial infection) Interacts with nipah virus and hendra virus glycoprotein.

Subcellular location. Membrane.

Tissue specificity. Highly expressed in brain; expressed in embryonic floor plate, roof plate and hindbrain segments.

Similarity. Belongs to the ephrin family.

RefSeq proteins (1): NP_001397* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001799	Ephrin_RBD	Domain
IPR008972	Cupredoxin	Homologous_superfamily
IPR019765	Ephrin_CS	Conserved_site
IPR031328	Ephrin	Family

Pfam: PF00812

UniProt features (18 total): compositionally biased region 2, modified residue 2, disulfide bond 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, glycosylation site 1, sequence variant 1, mutagenesis site 1, transmembrane region 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4BKF	X-RAY DIFFRACTION	4.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15768-F1	69.24	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 271, 274

Disulfide bonds (2): 62–104, 92–156

Glycosylation sites (1): 210

Mutagenesis-validated functional residues (1):

Position	Phenotype
124–125	complete loss of nipah protein g binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-3928664	Ephrin signaling
R-HSA-3928665	EPH-ephrin mediated repulsion of cells

MSigDB gene sets: 252 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, AGGAAGC_MIR5163P, MODULE_92, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEURON_RECOGNITION, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_FGF3, CHIBA_RESPONSE_TO_TSA_UP, GOBP_BEHAVIOR, GOBP_ADULT_BEHAVIOR, SP3_Q3, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_LYMPHOCYTE_COSTIMULATION

GO Biological Process (11): cell-cell signaling (GO:0007267), nervous system development (GO:0007399), axon guidance (GO:0007411), adult walking behavior (GO:0007628), axon choice point recognition (GO:0016198), T cell costimulation (GO:0031295), ephrin receptor signaling pathway (GO:0048013), negative regulation of axonogenesis (GO:0050771), trans-synaptic signaling by trans-synaptic complex, modulating synaptic transmission (GO:0099557), cell differentiation (GO:0030154), symbiont entry into host cell (GO:0046718)

GO Molecular Function (4): virus receptor activity (GO:0001618), transmembrane-ephrin receptor activity (GO:0005005), ephrin receptor binding (GO:0046875), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), presynaptic membrane (GO:0042734), hippocampal mossy fiber to CA3 synapse (GO:0098686), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
EPH-Ephrin signaling	3
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axonogenesis	2
cell communication	1
signaling	1
system development	1
neuron projection guidance	1
adult locomotory behavior	1
walking behavior	1
axon guidance	1
neuron recognition	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
cell surface receptor protein tyrosine kinase signaling pathway	1
negative regulation of neuron projection development	1
negative regulation of neurogenesis	1
regulation of axonogenesis	1
trans-synaptic signaling by trans-synaptic complex	1
trans-synaptic signaling, modulating synaptic transmission	1
cellular developmental process	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
ephrin receptor activity	1
signaling receptor binding	1
binding	1
membrane	1
cell periphery	1
synaptic membrane	1
presynapse	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
synapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1626 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EFNB3	EPHB6	O15197	998
EFNB3	EPHA4	P54764	998
EFNB3	EPHB2	P29323	995
EFNB3	EPHB3	P54753	991
EFNB3	EPHA1	P21709	986
EFNB3	EPHB1	P54762	982
EFNB3	EPHB4	P54760	968
EFNB3	DLG4	P78352	923
EFNB3	RGS3	P49796	878
EFNB3	NCK2	O43639	871
EFNB3	EPHA2	P29317	858
EFNB3	RHBDL2	Q9NX52	839
EFNB3	EPHA3	P29320	834
EFNB3	EPHA10	Q5JZY3	774
EFNB3	EPHA8	P29322	747

IntAct

160 interactions, top by confidence:

A	B	Type	Score
EPHA4	EFNB3	psi-mi:“MI:0407”(direct interaction)	0.780
EFNB3	EPHA4	psi-mi:“MI:0407”(direct interaction)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
EFNB3	DLG1	psi-mi:“MI:0407”(direct interaction)	0.590
PICK1	EFNB3	psi-mi:“MI:0407”(direct interaction)	0.590
PRKCSH	AURKA	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
IGSF8	CLGN	psi-mi:“MI:0914”(association)	0.530
FUCA2	HSPA5	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	EFNB3	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	HTRA2	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
EFNB3	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF11	EFNB3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (85): EFNB3 (Affinity Capture-MS), EFNB3 (Affinity Capture-MS), MPP7 (Affinity Capture-MS), EFNB3 (Affinity Capture-MS), EFNB3 (Affinity Capture-MS), EFNB3 (Affinity Capture-MS), DLG1 (Affinity Capture-MS), EFNB3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), FAM115C (Affinity Capture-MS), RTEL1 (Affinity Capture-MS), PLCD3 (Affinity Capture-MS), EFNB3 (Affinity Capture-MS), CDYL (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS)

ESM2 similar proteins: A2AIG8, A5D7H1, A6H7A0, A6NFX1, A6NJW4, A8MUP2, A8MXK1, B0BMW8, O35393, O54804, O73884, P01135, P35790, P52875, P57791, Q00961, Q01098, Q01134, Q06922, Q08DW9, Q0P5M9, Q0VDI3, Q14728, Q14957, Q15768, Q2M1K6, Q3UGX3, Q4R7M4, Q4V899, Q5E9H2, Q5M7U7, Q5R6I6, Q5RCI5, Q5ZI20, Q7TPB4, Q8BZH0, Q8IVW8, Q8N431, Q8NBA8, Q8R2R5

Diamond homologs: O08542, O08543, O08545, O35393, O43921, O73612, O73874, P20827, P52793, P52794, P52795, P52796, P52797, P52798, P52799, P52800, P52801, P52802, P52803, P52804, P79727, P79728, P97553, P97605, P98172, Q06AS9, Q15768, Q3ZC64, O13097

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
EFNB3	up-regulates	EPHA4	binding
EFNB3	up-regulates	EPHB3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	9	54.7×	1e-11
Unblocking of NMDA receptors, glutamate binding and activation	6	34.7×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	6	34.7×	2e-06
Long-term potentiation	6	30.4×	3e-06
Assembly and cell surface presentation of NMDA receptors	11	29.7×	2e-11
Dopamine Neurotransmitter Release Cycle	5	26.4×	5e-05
Neurexins and neuroligins	11	23.0×	2e-10
Protein-protein interactions at synapses	7	19.8×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	44.7×	9e-12
protein localization to synapse	6	35.4×	4e-06
receptor clustering	7	33.6×	5e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	22.9×	4e-05
protein-containing complex assembly	9	7.9×	3e-04
cell-cell adhesion	10	7.8×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

44 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1425 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7708433:A:AG	acceptor_gain	1.0000
17:7708434:G:GG	acceptor_gain	1.0000
17:7708528:G:GG	donor_gain	1.0000
17:7708628:T:G	acceptor_gain	1.0000
17:7708630:TCCA:T	acceptor_loss	1.0000
17:7708632:CAG:C	acceptor_loss	1.0000
17:7708736:CCAGG:C	donor_loss	1.0000
17:7708737:CAGG:C	donor_loss	1.0000
17:7708738:AGGTA:A	donor_loss	1.0000
17:7708739:GG:G	donor_loss	1.0000
17:7708740:GTA:G	donor_loss	1.0000
17:7708741:T:A	donor_loss	1.0000
17:7705718:GAG:G	donor_gain	0.9900
17:7706335:G:GT	donor_gain	0.9900
17:7708189:G:GT	donor_gain	0.9900
17:7708189:GGA:G	donor_gain	0.9900
17:7708190:GAG:G	donor_gain	0.9900
17:7708429:TCCCA:T	acceptor_loss	0.9900
17:7708430:CCCAG:C	acceptor_loss	0.9900
17:7708431:CCAGC:C	acceptor_loss	0.9900
17:7708432:CAGCC:C	acceptor_loss	0.9900
17:7708433:AGCC:A	acceptor_loss	0.9900
17:7708434:GC:G	acceptor_gain	0.9900
17:7708434:GCC:G	acceptor_gain	0.9900
17:7708434:GCCA:G	acceptor_gain	0.9900
17:7708434:GCCAC:G	acceptor_gain	0.9900
17:7708526:AA:A	donor_gain	0.9900
17:7708627:A:AG	acceptor_gain	0.9900
17:7708633:A:AG	acceptor_gain	0.9900
17:7708634:G:GT	acceptor_gain	0.9900

AlphaMissense

2141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7705701:T:A	W35R	1.000
17:7705701:T:C	W35R	1.000
17:7705702:G:C	W35S	1.000
17:7705703:G:C	W35C	1.000
17:7705703:G:T	W35C	1.000
17:7707959:T:C	F42L	1.000
17:7707960:T:C	F42S	1.000
17:7707960:T:G	F42C	1.000
17:7707961:C:A	F42L	1.000
17:7707961:C:G	F42L	1.000
17:7707990:C:A	P52H	1.000
17:7708002:A:T	D56V	1.000
17:7708008:T:C	L58P	1.000
17:7708014:T:C	L60P	1.000
17:7708019:T:A	C62S	1.000
17:7708019:T:C	C62R	1.000
17:7708020:G:A	C62Y	1.000
17:7708020:G:C	C62S	1.000
17:7708021:C:G	C62W	1.000
17:7708077:T:C	L81P	1.000
17:7708083:T:C	L83P	1.000
17:7708109:T:A	C92S	1.000
17:7708109:T:C	C92R	1.000
17:7708110:G:A	C92Y	1.000
17:7708110:G:C	C92S	1.000
17:7708140:T:C	L102P	1.000
17:7708145:T:A	C104S	1.000
17:7708145:T:C	C104R	1.000
17:7708146:G:A	C104Y	1.000
17:7708146:G:C	C104S	1.000

dbSNP variants (sampled 300 via entrez): RS1000399298 (17:7709213 G>C,T), RS1000428690 (17:7708895 C>T), RS1001392350 (17:7707656 CG>C), RS1002054481 (17:7706213 T>C), RS1002110858 (17:7707785 T>C), RS1002353827 (17:7705552 C>A), RS1002698389 (17:7705907 T>G), RS1002710201 (17:7709185 C>T), RS1002949605 (17:7708861 A>G,T), RS1003284406 (17:7707503 G>A), RS1003386132 (17:7710965 C>A), RS1003960837 (17:7710266 C>G), RS1004386410 (17:7709685 C>A,T), RS1005059952 (17:7710535 A>C), RS1005118408 (17:7704397 C>T)

Disease associations

OMIM: gene MIM:602297 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008757_28	Alcohol consumption	4.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	increases expression	2
abemaciclib	decreases expression	1
FR900359	affects phosphorylation	1
propionaldehyde	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
zinc chromate	decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
abrine	decreases expression	1
licochalcone B	increases expression	1
jinfukang	increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Coumestrol	decreases expression	1
Doxorubicin	decreases response to substance	1
Nickel	decreases expression	1
Niclosamide	increases expression	1
Oxygen	increases expression	1
Silicon Dioxide	decreases expression	1
Silver	decreases expression	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.